Neuroinflammation in schizophrenia: meta-analysis of in vivo microglial imaging studies

Abstract

Background: Converging lines of evidence implicate an important role for the immune system in schizophrenia. Microglia are the resident immune cells of the central nervous system and have many functions including neuroinflammation, axonal guidance and neurotrophic support. We aimed to provide a quantitative review of in vivo PET imaging studies of microglia activation in patients with schizophrenia compared with healthy controls.

Methods: Demographic, clinical and imaging measures were extracted from each study and meta-analysis was conducted using a random-effects model (Hedge's g). The difference in 18-kDa translocator protein (TSPO) binding between patients with schizophrenia and healthy controls, as quantified by either binding potential (BP) or volume of distribution (VT), was used as the main outcome. Sub-analysis and sensitivity analysis were carried out to investigate the effects of genotype, ligand and illness stage.

Results: In total, 12 studies comprising 190 patients with schizophrenia and 200 healthy controls met inclusion criteria. There was a significant elevation in tracer binding in schizophrenia patients relative to controls when BP was used as an outcome measure, (Hedge's g = 0.31; p = 0.03) but no significant differences when VT was used (Hedge's g = -0.22; p = 0.29).

Conclusions: In conclusion, there is evidence for moderate elevations in TSPO tracer binding in grey matter relative to other brain tissue in schizophrenia when using BP as an outcome measure, but no difference when VT is the outcome measure. We discuss the relevance of these findings as well as the methodological issues that may underlie the contrasting difference between these outcomes.

Keywords: Microglia; TSPO; neuroinflammation; schizophrenia.

Fig. 1.

Flowchart showing the inclusion of studies for the meta-analysis.

Fig. 2.

Forest plot showing the effect sizes for in vivo microglia measures in schizophrenia patients compared with controls as measured by translocator protein binding potential (BP) in total grey matter. There was a significant elevation in schizophrenia with an effect size = 0.31 (p = 0.03).

Fig. 3.

Forest plot showing effect sizes for in vivo microglia measures in schizophrenia patients compared with controls as measured by volume of distribution of translocator radiotracer (V_T) in total grey matter. There were no significant changes in patients compared with controls (effect size = −0.22, p = 0.296).